A number of naturally derived antitumor agents are now recognized to exert their effects by mediating DNA degradation. These include alkylating agents such as anthramycin and CC1065, compounds that mediate DNA cleavage (bleomycin, neocarzinostatin, esperamycin) and agents that stabilize cleavable complex formation in the presence of topoisomerases I or II (camptothecin, epipodophyllotoxins). The long term objectives of this work are the identification of additional natural products that mediate DNA cleavage and thereby exert antitumor activity. During the three year period of research proposed, the emphasis will be placed on the discovery of plant-derived natural products that: 1. cleave DNA by novel mechanisms 2. have demonstrable antitumor activity in vitro.